Safety of a Single Intravenous Dose of Recombinant Factor XIII in Children With Congenital FXIII A-subunit Deficiency

Phase 3

Completed

Conditions: Congenital Bleeding Disorder
Congenital FXIII Deficiency

Interventions: Drug: catridecacog

Registration Number: NCT01230021

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Europe and United States of America (USA). The aim of this clinical trial is to investigate the pharmacokinetics (at which rate the substance is distributed and eliminated from the body) and the safety profile of catridecacog (recombinant factor XIII (rFXIII)) in children with congenital FXIII A-subunit deficiency. Young children (1 to less than 6 years old) with congenital FXIII deficiency are evaluated.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

Inclusion Criteria

Signed Informed Consent by subject's parents or subject's legally acceptable representative before any trial related activities. Trial related activities are any procedures that would not have been performed during the normal management of the subject
Age 1 to less than 6 years old at the time of enrolment
Congenital FXIII subunit-A deficiency previously documented by genotyping or evaluated by genotyping through blood sampling at screening visit
Body weight at least 10 kg

Exclusion Criteria

Known antibodies to FXIII
Hereditary or acquired coagulation disorder other than FXIII A-subunit congenital deficiency
Platelet count (thrombocytes) of less than 50 × 10^9/L (at screening visit)
Previous history of autoimmune disorder involving autoantibodies e.g., systemic lupus erythematosus
Previous history of arterial or venous thromboembolic events e.g., cerebrovascular accident or deep vein thrombosis
Known or suspected allergy to trial product or related products
Any surgical procedure in the 30 days prior to enrolment and any planned surgery during the trial period
Any disease or condition which, judged by the Investigator, could imply a potential hazard to the subject or interfere with the trial participation or trial outcome including renal and/or liver dysfunction

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
recombinant factor XIII	catridecacog	-

Primary Outcome Measures

Name	Time	Method
Area Under the Concentration vs. Time Curve (AUC)	At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing	A measure of the exposure. Blood samples for the PK assessment were drawn pre-dose and up to 30 days after dosing. The PK of FXIII in children was assessed after a single i.v. dose of rFXIII 35 IU/kg.

Secondary Outcome Measures

Name	Time	Method
Area Under the Concentration vs. Time Curve (AUC0-∞)	From day 0 to day 30	A measure of exposure.
Maximum Plasma Concentration (Cmax) for FXIII	At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing	Maximum plasma concentration of the drug reached.
Terminal Half-life (t½)	From day 0 to day 30	Time point when half of the maximum plasma concentration is reached.
Mean Residence Time (MRT)	From day 0 to day 30	The mean residence time (MRT) of a drug in the body and related functions are derived for drugs which are intravenously administered.
Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds)	Day 0 and day 30
Coagulation Related Parameters - Prothrombin Time (PT) (Seconds)	Day 0 and day 30
Total Plasma Clearance (CL)	From day 0 to day 30	The total plasma clearance is a measure of the elimination of a drug from the body. Drugs are excreted primarily by the kidneys into the urine. Clearance is calculated as 'CL=Dose / AUC0-30 days').
Volume of Distribution at Steady State (Vss)	At steady state	Volume of distribution at steady state (Vss) is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state. Steady state is achieved when all variables are constant in spite of ongoing processes.
Percentage of Subjects With One or More Adverse Events (AEs) Recorded	From day 0 to day 30
Percentage of Subjects With One or More Serious Adverse Events (SAEs)	From day 0 to day 30
Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII)	At screening and day 30
Coagulation Related Parameters - Fibrinogen	Day 0 and at day 30
Clot Solubility Test (Evaluated as Normal/Abnormal)	Day 0 and day 30	Blood samples for clot solubility drawn at each visit (1 hour before and after dose administration). A clot solubility assay was used to screen for FXIII deficiency. The assay is based on the ability of urea to dissolve fibrin clots that have not undergone FXIII-induced stabilization. Normal blood clots generally remain stable for 24 hours or more, while clots in which fibrin molecules have not been cross-linked are soluble within minutes. The outcome of the test is normal (FXIII present; a clot is observed in the test tube) or abnormal (FXIII absent or very low level; no clot in test tube).
Vital Signs - Pulse	Day 0 and day 30
Vital Signs - Blood Pressure (Systolic and Diastolic)	Day 0 and day 30
Physical Examination (Evaluated as Normal/Abnormal)	From day 0 to day 30